Local anesthetics 2

Question 1

Select the true statement regarding the primary mechanism of action of local anesthetics.
a. the conjugate acid binds to the extracellular portion of the sodium channel
b. the conjugate acid binds to the intracellular portion of the sodium channel
c. the uncharged base binds to the extracellular portion of the sodium channel
d. the uncharged base binds to the intracellular portion of the sodium channels

Answer 1

b. conjugate acid binds to the intracellular portion of the sodium channel

Question 2

Local anesthetics are

Answer 2

weak bases

Question 3

After you inject local anesthetic around a nerve, the local anesthetic rapidly

Answer 3

dissociates into an uncharged base (LA) and an ionized conjugate acid (LA+)

Question 4

Since local anesthetics are weak bases with pKa values higher than 7.4, we can predict that

Answer 4

> 50% of the local anesthetic will exist as the ionized, conjugate acid

Question 5

Only ________- binds to the local anesthetic binding site

Answer 5

ionized, conjugate acid

Question 6

The sodium channel remains in the closed, inactivated state until

Answer 6

enough local anesthetic diffuses away; during this time it’s resistant to depolariziation

Question 7

Some of the non-ionized local anesthetic molecules diffuse thorugh

Answer 7

the lipid-rich axolemma
once inside, a new equilibrium between LA and La+ is established ;

Question 8

What 3 paths can a local anesthetic travel after it’s injected near a peripheral nerve?

Answer 8

1. diffuse into the nerve
2. diffuse into surrounding tissue and bind to neighboring proteins
3. diffuse into the systemic circulation

Question 9

A patient states she experienced hypotension, tachycardia, and shortness of breath after receiving tetracaine during a previous surgery. Which drugs should be avoided in this patient? (select 3)
a. benzocaine
b. chloroprocaine
c. EMLA cream
d. articaine
e. cocaine
f. mepivacaine

Answer 9

a. benzocaine
b. chloroprocaine
e. cocaine

Question 10

What are the two classes of local anesthetics?

Answer 10

esters & amides

Question 11

The local anesthetic molecule is constructed from three key components:

Answer 11

benzene ring
intermediate side chain
tertiary amine

Question 12

__________determines the local anesthetic’s drug class

Answer 12

the intermediate side chain

Question 13

The intermediate side chain determines how

Answer 13

each drug class is metabolized

Question 14

Amide-type local anesthetics are metabolized

Answer 14

in the liver by the P450 system

Question 15

Ester- type local anesthetics are metabolized

Answer 15

in the plasma by pseudocholinesterase

Question 16

What are the ester-type local anesthetics?

Answer 16

benzocaine
cocaine
chloroprocaine
procaine
tetracaine

Question 17

What are the amide-type local anesthetics?

Answer 17

bupivacaine
dibucaine
lidocaine
mepivacaine
ropivacaine

Question 18

All the amides have

Answer 18

two “i’s” in their names

Question 19

Although true allergy to local anesthetics is rare, it is more common with

Answer 19

esters due to PABA

Question 20

If a patient has experienced a true allergy with an ester, the safest course is to

Answer 20

change to a preservative free amide

Question 21

Is there cross sensitivity between esters and amides?

Answer 21

no

Question 22

What is PABA?

Answer 22

para-aminobenzoic acid
can be found in ester LA

Question 23

Which characteristics correlate BEST with local anesthetic duration of action?
a. protein binding
b. lipid solubility
c. pKa
d. concentration

Answer 23

a. protein binding

Question 24

What is the primary determinant of onset of action with LAs?

Answer 24

pKa

Question 25

What is the secondary determinants of onset of action with LAs?

Answer 25

dose and concentration

Question 26

What is the primary determinant of potency with LAs?

Answer 26

lipid solubility

Question 27

What are the secondary determinants of potency with LAs?

Answer 27

intrinsic dilating effects

Question 28

What is the primary determinant of duration of action?

Answer 28

plasma protein binding

Question 29

What is the secondary determinants of duration of action?

Answer 29

lipid solubility & addition of vasoconstrictors

Question 30

If the pKa of the local anesthetic is closer to the pH of the blood, then a larger fraction of molecules will exist as

Answer 30

the lipid-soluble uncharged base. More molecules diffusing across the axolemma translates to a faster onset of action

Question 31

If the pKa of the LA is further away from the pH of the blood, there will be

Answer 31

fewer molecules available to penetrate the cell membrane which prolongs the onset of action

Question 32

Explain why chloroprocaine is exception to the pKa & onset of action.

Answer 32

chloroprocaine has a high pKa in isolation this would suggest a slower onset; it is not very potent so large dose must be given creating a mass effect that has a rapid onset of action

Question 33

Agents that are more liphophilic tend to be

Answer 33

more potent and have longer durations of action

Question 34

Lipid solubility is increased with

Answer 34

alkyl group substitution on the amide group and the benzene ring

Question 35

At higher concentrations (what we clinically use), LAs cause

Answer 35

vasodilation which removes the LA from its site of action and contributes to the termination of its effect

Question 36

_________ is an exception to vasodilation because it inhibits NE reuptake and always causes vasoconstriction

Answer 36

cocaine

Question 37

The pKA correlates with

Answer 37

the onset of action

Question 38

The closer the pKa is to the pH of the blood, the ___________ the local anesthetic begins to take effect.

Answer 38

faster

Question 39

Is a local anesthetic an acid or a base?

Answer 39

weak base

Question 40

If you put a local anesthetic in an aqueous solution, a fraction

Answer 40

will remain non-ionized and the remaining fraction will ionize

Question 41

When the drug's pKa is closer to blood pH, then there's a higher amount of

Answer 41

uncharged base there's more drug that can diffuse through the axolemma

Question 42

What is the pKa of bupivacaine?

Answer 42

8.1

Question 43

What is the pKa of levobupivacaine?

Answer 43

8.1

Question 44

What is the pKa of ropivacaine?

Answer 44

8.1

Question 45

What is the pKa of lidocaine?

Answer 45

7.9

Question 46

What is the pKa of prilocaine?

Answer 46

7.9

Question 47

What is the pKa of mepivacaine?

Answer 47

7.6

Question 48

What is the pKa of procaine?

Answer 48

8.9

Question 49

What is the pKa of chloroprocaine?

Answer 49

8.7

Question 50

What is the pKa of tetracaine?

Answer 50

8.5

Question 51

_______________ does not undergo protein binding.

Answer 51

chloroprocaine

Question 52

The exception to the rule of the closer the pKa is to the pH of the blood, the faster the onset is

Answer 52

chloroprocaine

Question 53

All ester local anesthetics have __________ pKa values

Answer 53

higher (8.5-8.9)

Question 54

All amides have _________________ pKa values

Answer 54

lower (than the esters... highest is 8.1)

Question 55

What is the pH of benzocaine?

Answer 55

3.5

Question 56

The only local anesthetic with a pKa well below physiologic pH is

Answer 56

benzocaine

Question 57

With benzocaine, ____________________ is a significant risk

Answer 57

methemoglobinemia

Question 58

Benzocaine is useful for

Answer 58

topical anesthesia of mucus membranes during endoscopy, TEE placement, and bronchoscopy

Question 59

In an acidic solution, weak bases are:

Answer 59

more ionized and water soluble